title: Fluticasone uptake across Calu-3 cells is mediated by salmeterol when deposited as a combination powder inhaler.
abstract: OBJECTIVE
  We assessed whether co-deposition of a long-acting β2 -agonist and a corticosteroid affects their respective transport rates across epithelial cells.
  
  
  METHODS
  Drug particles were deposited on the air-interface culture of Calu-3 cells using a twin-stage impinger. We compared the transport rate of salmeterol and fluticasone across the epithelial cells using commercially available formulations (Serevent, Flixotide and Seretide). The transepithelial resistance of Calu-3 cells was measured before and after each deposition to monitor epithelial resistance.
  
  
  RESULTS
  The codeposition of salmeterol and fluticasone had no significant effect on transport of salmeterol through the cell layer. In contrast, the rate of fluticasone propionate transport in presence of salmeterol xinofoate was significantly lower (0.53 ± 0.20%) compared with the single fluticasone formulation (2.36 ± 0.97%). Furthermore, the resistance of the epithelial cells was significantly increased after salmeterol deposition from both single and combination products.
  
  
  CONCLUSIONS
  Our data demonstrate that salmeterol may decrease the permeability of epithelial cells, resulting in slower fluticasone transport across Calu-3 epithelial monolayers. The subsequent increased residence time of fluticasone in the airways could prolong its anti-inflammatory effects.
authors.affiliation: Respiratory Technology, The Woolcock Institute of Medical Research, Sydney, New South Wales, Australia; Discipline of Pharmacology, School of Medicine The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Mehra
authors.initials: M
authors.lastname: Haghi
authors.forename: Daniela
authors.initials: D
authors.lastname: Traini
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.forename: Mary
authors.initials: M
authors.lastname: Bebawy
authors.forename: Paul M
authors.initials: PM
authors.lastname: Young
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000493:pharmacokinetics; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000493:pharmacokinetics; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000730:Androstadienes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001980:Bronchi / Q000378:metabolism*; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000502:physiology*; D002478:Cells, Cultured; D004338:Drug Combinations; D058995:Dry Powder Inhalers; D004847:Epithelial Cells / Q000378:metabolism*; D000068298:Fluticasone; D006801:Humans; D066298:In Vitro Techniques; D000068299:Salmeterol Xinafoate; D057900:Transcytosis / Q000502:physiology
chemical_list: D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D000730:Androstadienes; D004338:Drug Combinations; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol
keywords: Calu-3; epithelial transport; fluticasone propionate; salmeterol xinofoate